Process for producing adamantanol and adamantanone

ABSTRACT

There is provided a process for producing adamantanol and adamantanone which comprises reacting adamantane and oxygen in the presence of an oxidation catalyst constituted of a rare earth metal salt and a promoter containing an element selected from group 4 to group 10 of the new Periodic Table, and it is made possible through the production process according to the present invention to produce 2-adamantanol and 2-adamantanone in a high selectivity, high efficiency and safety by oxidizing adamantane under a mild reaction condition.

TECHNICAL FIELD

[0001] The present invention relates to a process for selectivelyproducing adamantanol and adamantanone that are each an importantintermediate of starting raw material for a variety of pharmaceuticals,agrochemicals and industrial products among adamantane derivatives bymeans of oxidization of adamantane.

BACKGROUND ART

[0002] Adamantane is known as a highly symmetrical cage compound whichhas a chemical constitution same as the constitution unit of diamond.Adamantane as a chemical substance is characterized by its (1) lowenergy of molecular strain and excellent heat resistance, (2) highdissolvability of fat and oil due to high carbon density, (3) less odorin spite of its sublimation properties and the like. Accordingly,attention has been paid since 1980 age to its availability inpharmaceutical field for raw materials of therapeutic drug forparkinsonism and therapeutic drug for influenza. Moreover in recentyears, the characteristics such as heat resistance and transparency thatare imparted to adamantane derivatives have attracted special attentionin the fields of optical material such as photoresist for semiconductorproduction, magnetic recording medium, optical fiber, optical lens andoptical disc substrate material; functional materials such as heatresistant plastics, coating material and adhesive; cosmetics;lubricating oil and the like, thereby expanding the application of theadamantane derivatives. In addition, the demands thereof have increasedin the field of pharmaceuticals such as raw materials for anticancerdrug, cerebral function-improving agent, therapeutic drug forneurological disorder and antiviral drug.

[0003] The technology of converting a hydrocarbon compound into analcohol and a ketone through oxidation is technology of extremeindustrial importance from the viewpoint of effective utilization ofcarbon resources. Although there has been industrially appliedtechnology of producing an alcohol and a ketone from a monocyclicaliphatic compound such as cyclohexane, there has not yet been developedany technology of selectively efficiently producing a monohydric alcoholand a ketone through selective oxidation of a polycyclic aliphaticcompound bearing secondary or tertiary carbon atoms.

[0004] In recent years, 2-adamantanol and 2-adamantanone from amongadamantane derivatives have come to be spotlighted each as an importantintermediate of a variety of pharmaceuticals and functional materials.However in the case of producing an alcohol by reacting adamantane withan oxidizing agent, the tertiary carbon atoms present in four numbers inone molecule thereof predominantly react to form not only a monohydricalcohol but also a dihydric alcohol and a trihydric alcohol, therebymaking it impossible to selectively produce 2-adamantanol. In addition,2-adamantanone is produced only by a process in which adamantane isheated and reacted in concentrated sulfuric acid.

[0005] As technology of producing adamantanol by oxidizing adamantane,there is known the technology in which adamantane is oxidized withoxygen in the presence of an imide compound (such asN-hydroxyphthalimide or the like) as a catalyst and a transition metalcomplex as a promoter {refer to Japanese Patent Application Laid-OpenNo. 327626/1997 (Heisei 9)}. Nevertheless, this technology suffers fromlow selectivity to a monohydric alcohol.

[0006] Further as technology of producing an oxocompound derivative(such as ketone), there is disclosed the catalytic technology in which astrong acid is added to the above-mentioned phthalimide compound as acatalyst and a transition metal complex as a promoter {refer to JapanesePatent Application Laid-Open No. 309469/1998 (Heisei 10)}. However, thistechnology suffers from low selectivity to the objective product andbesides the formation of unfavorable byproducts such as1-hydroxyadamantanone, 1-adamantanone, 1,3-adamantanediol andadamantanediol.

[0007] On the other hand, as technology other than the use of theabove-mentioned phthalimide based catalyst, there is known a process forproducing an alcohol and a ketone which comprises reacting adamantane inthe presence of a transition metal complex having a porphyrin basedorganic compound as a ligand and of an aldehyde analogue {refer toJapanese Patent Application Laid-Open No. 87216/1997 (Heisei 9)}.Nevertheless, this process involves such problems as extremely low yieldof adamantanol as low as 4.6% and 2-adamantanone as low as 0.7%, lowselectivity to the objective products and besides the necessity for thecoexistence of an expensive aldehyde analogue as a reducing agent.

[0008] In addition, there is reported a process for producingadamantanol which comprises hydroxylating an adamantane analogue in thepresence of a ruthenium compound and hypochlorous acid or a salt thereof(refer to Japanese Patent Application Laid-Open No. 219646/2000).However, it is impossible for this process to selectively produce theobjective 2-adamantanol, since the principal alcohol products are1-adamantanol and 1,3-diadamantanol.

[0009] As technology for selectively producing 2-adamantanol, there ispublicly well known a process for experimentally producing the same inconcentrated sulfuric acid. For instance, it is reported by Schlatmannthat 2-adamantanol is obtained at a yield of 72% by maintaining1-adamantanol under heating at 30° C. for 12 hours in concentratedsulfuric acid {refer to Tetrahadronn: 24, 5361 (1968)}. There isproposed a process in which the reaction is put into practice under atwo stage temperature condition as improved technology for theabove-mentioned process wherein highly oxidative concentrated sulfuricacid is used also as a solvent {refer to Japanese Patent ApplicationLaid-Open No. 189564/1999 (Heisei 11)}. Although this process enhancesthe yield of adamantanone, the problems still remain unsolved in that alarge amount of concentrated sulfuric acid is used, thereby complicatingthe step of separation and refining after the reaction and at a the sametime, necessitating the use of expensive and corrosion-resistantequipment and a material.

DISCLOSURE OF THE INVENTION

[0010] An object of the present invention is to provide a process whichis capable of producing 2-adamantanol and 2-adamantanone in a highselectivity, high efficiency and safety by oxidizing adamantane under amild reaction condition.

[0011] In such circumstances, intensive extensive research andinvestigation were accumulated by the present inventors in order tosolve and eliminate the problems of the prior arts as mentionedhereinbefore and at the same time, produce 2-adamantanol and2-adamantanone in a high selectivity, high efficiency and safety. As aresult, it has been found that the above-mentioned object can beachieved by oxidizing adamantane in the presence of a specific oxidationcatalyst. Thus the present invention has been accomplished on the basisof the foregoing findings and information.

[0012] Specifically, the present invention provides a process forproducing adamantanol and adamantanone which comprises reactingadamantane and oxygen in the presence of an oxidation catalystconstituted of a rare earth metal salt and a promoter containing anelement selected from group 4 to group 10 of the new Periodic Table.

THE MOST PREFERRED EMBODIMENT TO CARRY OUT THE INVENTION

[0013] As mentioned hereinabove, the oxidation catalyst to be used inthe production process according to the present invention comprises aprincipal catalyst constituted of a rare earth metal salt and a promotercontaining an element selected from group 4 to group 10 of the newPeriodic Table (in particular, group IVA to VIA and group VIII of theold Periodic Table).

[0014] The rare earth metal to be used therein is not specificallylimited, but is exemplified preferably by europium, ytterbium, samariumand the like.

[0015] Examples of the rare earth metal salt preferably include achloride of the above-mentioned rare earth metal andtrifluoromethanesulfonium salt.

[0016] The amount of the principal catalyst to be used is at least 0.5mol %, preferably at least 1.0 mol % based on adamantane as the reactionsubstrate. The amount to be used, when being less than 0.5 mol % basedthereon, brings about failure in a sufficient reaction rate, whereas alarger amount thereof does not exert influence upon the reaction.

[0017] It is possible in the process according to the present inventionto employ as a promoter, any of a variety of compounds containing anelement selected from among group 4 to group 10 of the new PeriodicTable. In particular, it is preferable that the catalyst systemcomprises an oxide complex containing an element selected from amongtitanium, cobalt, vanadium, chromium and manganese each belonging to anyof group 4 to group 7 of the new Periodic Table, for instance, atitanium oxide complex; and a compound of a metal selected from amongpalladium, platinum, rhodium and nickel each belonging to any of group 8to group 10 of the new Periodic Table, for instance, platinum oxide.

[0018] With regard to the promoter, the above-mentioned at least twokinds of compounds of a metal or metals may be used by being separatelysupported on each of catalyst carriers, or may be used as a compositecarrier wherein the at least two kinds of compounds are supported inturn on one catalyst carrier. Examples of the aforesaid catalystcarriers include a porous carrier such as active carbon, zeolite,silica, silica-alumina and bentonite.

[0019] In the case where two kinds of compounds of a metal or metals isused, various combinations thereof are available, including forinstance, preferable combination of titanium oxide-acetylacetonatocomplex and platinum oxide supported catalyst. In this case, theabove-mentioned titanium oxide-acetylacetonato complex and platinumoxide supported catalyst each as a promoter may be used alone, or as acomposite carrier wherein the titanium oxide-acetylacetonato complex issupported on the platinum oxide supported catalyst. The method ofsupporting metal species on a catalyst carrier is not specificallylimited, but is exemplified by an ordinary impregnation method.

[0020] The amount of the promoter containing a metal or metals selectedfrom among group 4 to group 7 of the new Periodic Table is at least 0.3mol %, preferably at least 1.0 mol % based on adamantane as the reactionsubstrate. The amount to be used, when being less than 0.3 mol % basedthereon, brings about failure in a sufficient reaction rate, whereas alarger amount thereof does not exert influence upon the reaction.

[0021] The amount of the promoter containing a metal or metals selectedfrom among group 8 to group 10 of the new Periodic Table on the basis ofactive metal compound is at least 0.007 part by weight, preferably atleast 0.010 part by weight each based on adamantane as the reactionsubstrate. The amount to be used, when being less than 0.007 part byweight based thereon, brings about failure in a sufficient reactionrate, whereas a larger amount thereof does not exert influence upon thereaction.

[0022] It is preferable in the production process according to thepresent invention to proceed with reaction by adding hydrogen as anactivating agent for oxygen molecules to the reaction system, wherehydrogen molecules are utilized as activating reducing agent for theoxygen molecules.

[0023] The reaction solvent to be used therein is not specificallylimited provided that it does not react with hydrogen and oxygen and atthe same time, adamantane is soluble therein, and is exemplified byacetic acid and ethyl acetate as a usable reaction solvent.

[0024] The amount of the reaction solvent to be used is 1 to 300 partsby weight, preferably 3 to 200 parts by weight each based on 1 part byweight of adamantane. An amount thereof to be used, when being less than1 part by weight based thereon, sometimes gives rise to deposit ofadamantane as the reaction substrate, whereas an amount thereof, whenbeing more than 300 parts by weight based thereon, leads to loweredreaction rate.

[0025] In addition, hydrogen and oxygen are supplied to the reactionsystem each in the form of gas under atmospheric pressure. The supplyratio of oxygen/hydrogen is in the range of 0.1 to 10, preferably 1 to3. A ratio thereof, when being less than 0.1, allows a side reaction offorming water to proceed, whereas a ratio thereof, when being more than10, brings about a marked decrease in reaction rate.

[0026] Further, the reaction temperature is in the range of 0 to 110°C., preferably 30 to 80° C. The reaction time is in the range of 0.5 to5 hours, preferably 1 to 3 hours.

EXAMPLES

[0027] In what follows, the present invention will be described in moredetail with reference to comparative examples and working examples,which however shall never limit the present invention thereto.

[0028] The hydrogen activation promoters which were used in thefollowing working examples were each prepared by impregnating andsupporting any of various metals each of which belonged mainly to anoble metal and had hydrogen dissociation/adsorption function into andon a carrier, and then subjecting the metal to a firing or reducingtreatment. In the following, some description will be given as typicalexamples, of methods for preparing a catalyst (PtO_(X)/SiO₂) whereinplatinum was supported on silica as the carrier and a composite catalyst{(TiO(acac)_(Z)/PtO_(X)/SiO₂} wherein acac denotes acetyl acetonato.

Reference Example 1

[0029] {Preparation of 1 wt %-PtO_(X)/SiO₂ (SIO-8) promoter}

[0030] To 850 milliliter (mL) of ion exchange water in a 300 mL of abeaker was added 4950 g of SiO₂ (Reference Catalyst JRC-SIO-8 of TheInstitute of Catalyst), and 13.4 mL of 1.91 mol/liter of aqueoussolution of H₂PtCl₄ was added dropwise in the beaker by means of aburette under heating and stirring. The resultant mixture was evaporatedto bone dryness under vigorous stirring, further sufficiently dried andthereafter, fired in a muffle furnace at 150° C. for 2 hourssubsequently at 300° C. for 4 hours to obtain PtO_(X)/SiO₂ (SIO-8)promoter.

Reference Example 2

[0031] {Preparation of TiO(acac)₂/PtO_(X)/SiO₂ catalyst}

[0032] To 20 mL of acetic acid in a 100 mL of a beaker was added 20 μmolof TiO(acac)₂ under heating and stirring to completely dissolve it.Thereafter 500 mg of 1 wt %-PtO_(X)/SiO₂ which had been prepared inadvance was added in the beaker. The resultant mixture was evaporated tobone dryness on a hot plate at 150° C. under vigorous stirring, andfurther sufficiently dried. Thereafter, the dried product was used forthe reaction as such without treatment in particular. In the following,the reaction was put into practice by varying the amount of the titaniumoxide acetyl acetonato {TiO(acac)₂} to be added in accordance with theamount of the titanium oxide acetyl acetonato to be supported.

Example 1

[0033] A 100 mL of three neck round bottom flask which had been equippedwith a stirrer, a thermometer and a Dimroth condenser was charged with0.136 g (1 mmol), 1.29 mg (5 μmol) of europium chloride, 0.86 mg (3.3μmol) of titanium oxide acetyl acetonato each as the catalyst, 0.1 g ofplatinum oxide supported catalyst and 20 mL of acetic acid as thesolvent to proceed with the reaction at 40° C. for 2 hours, whilepassing a mixed gas of hydrogen and oxygen through the flask at a flowrate of 20 mL/min at a hydrogen partial pressure of 75.9 kPa and anoxygen partial pressure of 25.4 kPa.

[0034] After the completion of the reaction, the produced liquid wasanalyzed by means of gas chromatogram (available from Shimadzu GC-14Acolumn, PEG=20 M, capillary column). As a result, there were obtained asthe objective products, 93.8 μmol of 1-adamantanol, 22.2 μmol of2-adamantanone and 75.7 μmol of 2-adamantanol at a yield of 19.2% withselectivity to 2-adamantanone and 2-adamantanol of 51.1%. Theperformance results are given in Table 1.

Example 2

[0035] The procedure in Example 1 was repeated to prepare the productsexcept that europium chloride was used in an amount of 2.59 mg (10μmol). The results are given in Table 1.

Example 3

[0036] The procedure in Example 1 was repeated to prepare the productsexcept that europium chloride was used in an amount of 5.17 mg (20μmol). The results are given in Table 1.

Example 4

[0037] The procedure in Example 1 was repeated to prepare the productsexcept that europium chloride was used in an amount of 15.51 mg (60μmol). The results are given in Table 1.

Example 5

[0038] The procedure in Example 1 was repeated to prepare the productsexcept that europium chloride was used in an amount of 31.02 mg (120μmol). The results are given in Table 1.

Example 6

[0039] The procedure in Example 2 was repeated to prepare the productsexcept that titanium oxide acetyl acetonato was used in an amount of5.24 mg (20 μmol). The results are given in Table 1.

Example 7

[0040] The procedure in Example 3 was repeated to prepare the productsexcept that titanium oxide acetyl acetonato was used in an amount of5.24 mg (20 mol). The results are given in Table 1.

Example 8

[0041] The procedure in Example 4 was repeated to prepare the productsexcept that titanium oxide acetyl acetonato was used in an amount of5.24 mg (20 μmol). The results are given in Table 1.

Example 9

[0042] The procedure in Example 6 was repeated to prepare the productsexcept that titanium oxide acetyl acetonato was used in an amount of31.02 mg (120 μmol). The results are given in Table 1.

Example 10

[0043] The procedure in Example 9 was repeated to prepare the productsexcept that adamantane and titanium oxide acetyl acetonato were used inamounts of 0.272 g (2 mmol) and 0.86 mg (3.3 μmol), respectively. Theresults are given in Table 1.

Example 11

[0044] The procedure in Example 9 was repeated to prepare the productsexcept that adamantane was used in an amount of 0.272 g (2 mmol). Theresults are given in Table 1.

Example 12

[0045] The procedure in Example 1 was repeated to prepare the productsexcept that use was made of 0.1 g of platinum oxide catalyst supporting20 μmol of titanium oxide acetyl acetonato. The results are given inTable 1.

Example 13

[0046] The procedure in Example 1 was repeated to prepare the productsexcept that use was made of 0.1 g of platinum oxide catalyst supporting3.3 μmol of titanium oxide acetyl acetonato. The results are given inTable 1.

Comparative Example 1

[0047] The procedure in Example 1 was repeated to prepare the productsexcept that europium chloride was not used in the reaction. The resultsare given in Table 1.

Comparative Example 2

[0048] The procedure in Example 6 was repeated to prepare the productsexcept that europium chloride was not used in the reaction. The resultsare given in Table 1.

Comparative Example 3

[0049] The procedure in Example 1 was repeated to prepare the productsexcept that europium chloride and titanium oxide acetyl acetonato werenot used in the reaction. The results are given in Table 1.

Comparative Example 4

[0050] The procedure in Example 3 was repeated to prepare the productsexcept that titanium oxide acetyl acetonato was not used in thereaction. The results are given in Table 1.

Comparative Example 5

[0051] The procedure in Example 3 was repeated to prepare the productsexcept that a hydrogen activation promoter was not used in the reaction.The results are given in Table 1. TABLE 1 Charge TiO- (acac)₂/ PtOx/PtOx/SiO₂ Adamantane EuCl₃ TiO(acac)₂ SiO₂ (μmol)/ (mmol) (μmol) (μmol)(g) (g) Example 1 1 5 3.3 0.1 — Example 2 1 10 3.3 0.1 — Example 3 1 203.3 0.1 — Example 4 1 60 3.3 0.1 — Example 5 1 120 3.3 0.1 — Example 6 110 20 0.1 — Example 7 1 20 20 0.1 — Example 8 1 60 20 0.1 — Example 9 1120 20 0.1 — Example 10 2 120 3.3 0.1 — Example 11 2 120 20 0.1 —Example 12 1 20 — — 20/0.1 Example 13 1 20 — — 20/0.1 Comparative 1 0 200.1 0.1 Example 1 Comparative 1 0 0 0.1 0.1 Example 2 Comparative 1 0 00.1 0.1 Example 3 Comparative 1 20 20 0.1 0.1 Example 4 Comparative 1 2020 0 — Example 5 Reaction Performance Product (μmol) Yield 1 - OH 2 -AdO 2 - AdOH (%) Selectivity (%) Example 1 93.8 22.2 75.7 19.2 51.1Example 2 114.7 36.6 81.2 23.2 50.6 Example 3 151.6 75.9 71.1 29.9 49.2Example 4 157.2 108.3 56.4 32.2 51.2 Example 5 158.3 136.0 47.2 34.153.6 Example 6 147.4 57.9 74.4 28 47.3 Example 7 152.2 72.7 66.5 29.147.8 Example 8 179.9 129.7 54.5 36.4 50.6 Example 9 162.0 149.3 38.7 3553.7 Example 10 261.7 104.0 121.3 24.3 46.3 Example 11 350.0 215.4 87.232.6 46.4 Example 12 168.8 86.2 63.5 31.9 47.0 Example 13 165.6 76.089.5 33.1 50.0 Comparative 9.3 20.0 8.4 1.8 47.5 Example 1 Comparative22.2 5.7 10.8 3.9 42.6 Example 2 Comparative 1.8 0 1.0 0.3 36.3 Example3 Comparative 11.5 0 12.4 2.4 51.9 Example 4 Comparative 0.8 0 0 0 0Example 5

[0052] {Remarks}

[0053] 1-OH: 1-adamantanol, 2-AdO: 2-adamantanone, 2-AdOH:2-adamantanol,

Yield=Amount of product(μmol)/charged raw material(μmol)×100(%)

Selectivity={(Amount of produced 2-AdO(μmol)+(Amount of produced2-AdOH(μmol)}/amount of product(μmol)×100(%)

[0054] Industrial Applicability

[0055] According to the production process of the present invention, itis made possible to produce in a high selectivity, high efficiency andsafety, 2-adamantanol and 2-adamantanone that are useful in the fieldsof pharmaceuticals and agrochemicals, semiconductors, magnetic recordingmedia, optical materials, heat resistant plastics, coating materials,adhesives, cosmetics, lubricating oils and the like by oxidizingadamantane under a mild reaction condition. In addition according to theproduction process of the present invention, since no corrosivesubstance is used in the reaction system, it is not necessary to use anyexpensive and corrosion-resistant equipment and a material and at thesame time, the step of separation and refining after the reaction issimplified.

1. A process for producing adamantanol and adamantanone which comprisesreacting adamantane and oxygen in the presence of an oxidation catalystconstituted of a rare earth metal salt and a promoter containing anelement selected from group 4 to group 10 of the new Periodic Table. 2.The process for producing adamantanol and adamantanone according toclaim 1, wherein the rare earth metal is europium, ytterbium or samariumwhich are each trivalent.
 3. The process for producing adamantanol andadamantanone according to claim 1, wherein the promoter in the catalystsystem comprises a compound of a metal selected from among titanium,cobalt, vanadium, chromium and manganese each belonging to any of group4 to group 7 of the new Periodic Table, and a compound of a metalselected from among palladium, platinum, rhodium and nickel eachbelonging to any of group 8 to group 10 of the new Periodic Table, 4.The process for producing adamantanol and adamantanone according toclaim 1, wherein hydrogen is added to reactants as an activating agentfor oxygen molecules.